Lung Cell Fiber Evanescent Wave Spectroscopic Biosensing of Inhalation Health Hazards Mark R. Riley, 1 Pierre Lucas, 2 David Le Coq, 3 Christophe Juncker, 2 Dianne E. Boesewetter, 1 Jayne L. Collier, 1 Diana M. DeRosa, 1 Matthew E. Katterman, 1 Catherine Boussard-Ple ´ del, 4 Bruno Bureau 4 1 Department of Agricultural and Biosystems Engineering, University of Arizona, Tucson, Arizona 85721; telephone: 520-626-9120; fax: 520-621-3963; e-mail: riley@ag.arizona.edu 2 Department of Material Science and Engineering, University of Arizona, Tucson, Arizona 85721. 3 Laboratoire de physicochimie de l’atmosphe `re, Universite du Littoral, 59140 Dunkerque, France 4 Laboratoire des Verres et Ce ´ramiques, UMR-CNRS 6512, Universite ´ de Rennes 1 Campus de Beaulieu, 35042 Rennes, France Received 8 August 2005; accepted 14 February 2006 Published online 9 August 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/bit.21152 Abstract: Health risks associated with the inhalation of biological materials have been a topic of great concern; however, there are no rapid and automatable methods available to evaluate the potential health impact of inhaled materials. Here we describe a novel approach to evaluate the potential toxic effects of materials evaluated through cell-based spectroscopic analysis. Anchorage-dependent cells are grown on the surface of optical fibers transparent to infrared light. The probe system is composed of a single chalcogenide fiber (composed of Te, As, and Se) acting as both the sensor and transmission line for infrared optical signals. The cells are exposed to potential toxins and alterations of cellular composition are monitored through their impact on cellular spectral features. The signal is collected via evanescent wave absorption along the tapered sensing zone of the fiber through spectral changes between 3,000 and 600 cm 1 (3,333–16,666 nm). Cell physiology, composition, and function are non-invasively tracked through monitoring infrared light absorption by the cell layer. This approach is demon- strated with an immortalized lung cell culture (A549, human lung carcinoma epithelia) in response to a variety of inhalation hazards including gliotoxin (a fungal meta- bolite), etoposide (a genotoxin), and methyl methanse- sulfonate (MMS, an alkylating agent). Gliotoxin impacts cell metabolism, etoposide impacts nucleic acids and the cell cycle, and MMS impacts nucleic acids and induces an immune response. This spectroscopic method is sensi- tive, non-invasive, and provides information on a wide range of cellular damage and response mechanisms and could prove useful for cell response screening of pharma- ceuticals or for toxicological evaluations. ß 2006 Wiley Periodicals, Inc. Keywords: FTIR spectroscopy; chalcogenide glass fiber; human lung cells; cell culture; toxicity monitoring INTRODUCTION Concern for the risks associated with inhalation of hazardous materials has been raised due to several highly-publicized cases of human exposure to anthrax, to increased under- standing of the health effects of inhaled particulate matter, and to increased concerns of indoor air pollution. When the identity and composition of the potential toxin are unknown, this often requires extensive and expensive analysis using numerous laboratory animals. Such methods cannot provide suitable monitoring of the health impact of transient factors. The lack of a rapid means to directly quantify the health impact of inhalation hazards has led to the development of environmental regulations based on easily quantified metrics, such as the mass of particulate matter, which do not directly correlate to health risks. To address the need for a means to monitor the potential impact of inhaling air of dubious quality, cell-based biosensing devices are being developed utilizing cell cultures that are responsive to many common inhalation hazards. These portable devices contain living biological cells that respond through physiological changes induced by exposure to environmental hazards including toxicants, pathogens, or other agents [Stenger et al., 2001]. Such an approach can evaluate the potential toxicity of compounds relatively quickly, outside of the laboratory environment, inexpen- sively, and without the need for highly trained technicians. ß 2006 Wiley Periodicals, Inc. Correspondence to: M.R. Riley Contract grant sponsors: DARPA; NIEHS; Arizona Board of Regents Technology and Research Initiative Fund Contract grant numbers: 66001- C-8041; P30 ES06694